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Transcriptional landscape of human microglia implicates age, sex, and APOE-related immunometabolic pathway perturbations.

Tulsi PatelTroy P CarnwathXue WangMariet AllenSarah J LincolnLaura J Lewis-TuffinZachary S QuicksallShu LinFrederick Q Tutor-NewCharlotte C G HoYuhao MinKimberly G MalphrusThuy T NguyenElizabeth MartinCesar A GarciaRawan M AlkharbooshSanjeet GrewalKaisorn ChaichanaRobert WharenHugo Guerrero-CazaresAlfredo Quinones-HinojosaNilüfer Ertekin-Taner
Published in: Aging cell (2022)
Microglia have fundamental roles in health and disease; however, effects of age, sex, and genetic factors on human microglia have not been fully explored. We applied bulk and single-cell approaches to comprehensively characterize human microglia transcriptomes and their associations with age, sex, and APOE. We identified a novel microglial signature, characterized its expression in bulk tissue and single-cell microglia transcriptomes. We discovered microglial co-expression network modules associated with age, sex, and APOE-ε4 that are enriched for lipid and carbohydrate metabolism genes. Integrated analyses of modules with single-cell transcriptomes revealed significant overlap between age-associated module genes and both pro-inflammatory and disease-associated microglial clusters. These modules and clusters harbor known neurodegenerative disease genes including APOE, PLCG2, and BIN1. Meta-analyses with published bulk and single-cell microglial datasets further supported our findings. Thus, these data represent a well-characterized human microglial transcriptome resource and highlight age, sex, and APOE-related microglial immunometabolism perturbations with potential relevance in neurodegeneration.
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